In patients with chronic kidney disease (CKD), phosphate retention may contribute to progression of renal failure and is a major factor in the development of secondary hyperparathyroidism and vascular calcification. Progression of injury is causally associated with risk of mortality that is estimated 10 to 30 times higher for CKD patients undergoing dialysis than the general population. In fact, death is a more common outcome than dialysis or transplantation in patients with CKD. Phosphate binders are clinical mainstays in reducing dietary phosphate absorption and preventing hyperphosphatemia in the roughly 370,000 end-stage renal disease (ESRD) patients in the United States. While medicines exist that bind phosphorus effectively, all current forms of phosphate binder therapy are associated with very poor patient compliance due to a host of problems, including side effects that run the gamut of poor taste, halitosis, gastric bloating, constipation, the number of pills, and cost. Thus, there is great need for a better phosphate binder, defined as one which is both effective and taken by patients with high compliance. Preliminary studies indicate that a novel phosphate binder comprising combinations of calcium succinate and magnesium R-(+)-1-lipoate binds phosphate effectively at reasonable cost. The proposed Phase I STTR research will use a translational animal model to verify these preliminary results and determine whether this combination of salts concomitantly decreases the rate and progression of vascular calcification, attenuates adynamic bone disorder, and reduces inflammation and oxidative stress. In addition, activity will be compared to that of sevelamer carbonate, a standard of care for treatment of hyperphosphatemia in CKD patients in the U.S. End-stage renal disease (ESRD), already a major public health problem in the US, is increasing in incidence and prevalence. Today, treatment of hyperphosphatemia with phosphate binders costs patients, taxpayers, insurance companies, and the government over $1.2 billion a year. That cost would increase 2-3 times if all ESRD patients used non-calcium containing Pi binders. If successful, the proposed STTR Phase I research will confirm the usefulness of this approach for significantly enhanced treatment of the hyperphosphatemia and bone dysfunction of Stage 5 CKD. The approach has the potential to delay use of non-calcium containing Pi binders by extending the time of useful calcium-based phosphate binder therapy, thereby enabling a cost savings estimated at over $1 billion a year. PUBLIC HEALTH RELEVANCE: Kidney failure, already a major public health problem in the US, is becoming more common. People with kidney disease use phosphate binders to decrease phosphate intake from the food they eat. This prevents high blood phosphate levels. Current phosphate binders have side effects that make them poorly tolerated by the patients who use them, thus reducing their effectiveness. The proposed STTR Phase I research critically evaluates the usefulness of a new phosphate binder having the potential to correct high blood phosphate levels, improve the patient's quality of life, and yield significant cost savings to the patient, the health care system, and American taxpayers.